| ALI refers to an intensive clinical syndrome characterized by hypoxemia, non cardingcnic pulmonary edema, small pulmonary atelectasislow lung compliance and widespread capillary leakage. The severe stage of ALI is defined as acute respiratory distress syndrome (ARDS). According to the diagnostic criteria raised by Europe and the United States Joint Conference in1994, the incidences of ALI and ARDS in USA are79/100000and59/100000respectively in2005, leading to the enormous economic burden on families and society. It would be beneficient to patients with ALI to investigate the underlying pathogenesis of ALI and explore the effective therapeutic strategies.Primary ALI/ARDS is mostly caused by infectious pneumonia in China. As one of the most capital pathogens in community-and hospital-acquired pneumonia. Staphylococcus aureus (SA) often results in severe pulmoary infection and acute lung injury with a high mortality rate. Our project focuses on how to reduce the lung tissue damage caused by SA.Curcumin is a phenol pigment abstracted from curcuma genus of the ginger family. Cureumin is well-known to have many effects, such as anti-inflammation, anti-tumor. anti-microbes, antioxidantion, and so on. However, it is not clear that its role in the prevention of SA-induced ALI. By establishing a mouse model with ALI induced by SA, we explore the effects of curcumin on ALI and the related molecular mechanisms.Objective:The aim of this study is to investigate the effects of curcumin on SA-induced ALI in a mouse model and assess its related underlying mechanisms.Methods:8week old of C57/BL6female mice were randomly divided into three groups. Group-I:control group; Group-II:1×108CFU of SA was administered by intratracheal instillation; Group-Ⅲ:pretreatment of curcumin (50mg/kg) by intraperitoneal injection2h before SA instillation. Survival rates of three groups were observed. In addtion, mice were sacrificed at different time points. The lungs were removed for pathological examination (12h after infection), assessment of pulmonary vascular leakage, CFU counts, the expression of pro-and anti-inflammatory cytokines by PCR, and the protein expression of Erk, PAI-1, HMGB-1by Western Blot. Bronchoalveolar lavage fluid (BALF) was harvested for couting the number of total white cells and neutrophils, detecting cytokine production. The phosphorylation of IkB in BMMs was detected. The survival rate of mice intraperitoneally administered of anti-HMGB1(30μg/mice)5min before SA instillation was also observed.Results:An ALI mouse model was successfully established and confirmed by mouse general state, pathological examination, expression of inflammatory cytokines, pulmonary vascular permeability and pulmonary edema. Compared with SA model group, pretreatment of curcumin significantly alleviated lung neutrophil infiltration and vascular leakage, decreased the number of totle white cells and neutrophils in BALF (P<0.01), inhibited the expression of PAI-1and HMGB1(P<0.01). Curcumin also reduced the release of inflammatory cytokines including KC, MIP-2, TNF-a, IL-1β, and etc (P<0.05). whereas increased the expression of anti-inflammation factors such as SOCS1, CD200(P<0.01). The phosphorylation levels of Erkl/2and p-IkB were decreased by curcumin. Curcumin aslo decreased HMGB-1expression at the earlystage after SA infection. Furthermore, neutralizing antibodies of HMGB-1can improve the suvival rate of mice with ALI induce d by SA (P<0.05)Conclusion:Curcumin pretreatment has a protective effect on SA-induced acute lung injury in mice. The underlying mechanisms may be due to inhibit neutrophil recruitment, alleviate pulmonary vascular leakage, reduce the expression of PAI-1and HMGB-1, upregulate the anti-inflammation factors, and downregulate the inflammatory cytokines. Pretreatment of HMGB-1antibody can improve the suvival rate of ALI mice. |
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